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(Hypertension. 2001;37:1492.)
© 2001 American Heart Association, Inc.

Scientific Contributions

A Defect in Glycogen Synthesis Characterizes Insulin Resistance in Hypertensive Patients With Type 2 Diabetes

Anna Solini; Francesco Di Virgilio; Paola Chiozzi; Paola Fioretto; Angela Passaro; Renato Fellin

From the Department of Clinical and Experimental Medicine (A.S., A.P., R.F.) and Section of General Pathology (F.D.V., P.C.), University of Ferrara, Ferrara, Italy; and Department of Internal Medicine (P.F.), University of Padova, Padova, Italy.

Correspondence to Anna Solini, MD, PhD, Department of Clinical and Experimental Medicine, Section of Internal Medicine II, Via Savonarola, 9, I-44100 Ferrara, Italy. E-mail sli{at}dns.unife.it

Abstract—A subgroup of patients with type 2 diabetes shows a clustering of abnormalities such as peripheral insulin resistance, hypertension, and microalbuminuria. To evaluate whether these traits reflect intrinsic disorders of cell function rather than in vivo environmental effects, we studied a group of 7 nondiabetic hypertensive subjects with an altered albumin excretion rate (AER) (HyMA+) and 3 groups of patients with type 2 diabetes: 7 with normal blood pressure and normal AER (DH-MA-), 7 with high blood pressure and normal AER (DH+MA-), and 7 with both high blood pressure and altered AER (DH+MA+). Glucose disposal was measured during an hyperinsulinemic clamp (40 mU · m^2-1 · min^-1) with primed deuterated [6.6 ²H₂] glucose infusion. In the same subjects, a skin biopsy was performed and the following parameters were investigated: glucose transport (as determined by [³H]2-deoxyglucose uptake); glycogen synthase activity (as determined by [¹⁴C] glucose incorporation from UDP-[U-¹⁴C] glucose into glycogen); glycogen phosphorylase activity (as measured by the incorporation of [U-¹⁴C]glucose 1-phosphate into glycogen); and total glycogen content. In vivo glucose disposal was significantly reduced in DH+MA- and DH+MA+, with respect to DH-MA-, HyMA+, and controls. Insulin-stimulated glucose transport was similar in the 3 groups of patients with diabetes. A significant reduction of intracellular glycogen content was observed in DH+MA- and DH+MA+ compared with DH-MA- in both basal and insulin-stimulated conditions, probably because of a major impairment of glycogen synthase activity. Glycogen phosphorylase activity did not show differences between the groups. These results suggest that (1) the combination of type 2 diabetes with hypertension and altered AER is associated with impaired insulin sensitivity, and (2) intrinsic, possibly genetic, factors may account for increased peripheral insulin resistance in hypertensive microalbuminuric patients with type 2 diabetes, pointing to the reduction of glycogen synthase activity as a shared common defect.

Key Words: blood pressure • diabetes • insulin resistance • glycogen synthase • fibroblasts

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